Integrative multi-omics analysis unravels the host response landscape and reveals a serum protein panel for early prognosis prediction for ARDS.

BACKGROUND: The multidimensional biological mechanisms underpinning acute respiratory distress syndrome (ARDS) continue to be elucidated, and early biomarkers for predicting ARDS prognosis are yet to be identified. METHODS: We conducted a multicenter observational study, profiling the 4D-DIA proteomics and global metabolomics of serum samples collected from patients at the initial stage of ARDS, alongside samples from both disease control and healthy control groups. We identified 28-day prognosis biomarkers of ARDS in the discovery cohort using the LASSO method, fold change analysis, and the Boruta algorithm. The candidate biomarkers were validated through parallel reaction monitoring (PRM) targeted mass spectrometry in an external validation cohort. Machine learning models were applied to explore the biomarkers of ARDS prognosis. RESULTS: In the discovery cohort, comprising 130 adult ARDS patients (mean age 72.5, 74.6% male), 33 disease controls, and 33 healthy controls, distinct proteomic and metabolic signatures were identified to differentiate ARDS from both control groups. Pathway analysis highlighted the upregulated sphingolipid signaling pathway as a key contributor to the pathological mechanisms underlying ARDS. MAP2K1 emerged as the hub protein, facilitating interactions with various biological functions within this pathway. Additionally, the metabolite sphingosine 1-phosphate (S1P) was closely associated with ARDS and its prognosis. Our research further highlights essential pathways contributing to the deceased ARDS, such as the downregulation of hematopoietic cell lineage and calcium signaling pathways, contrasted with the upregulation of the unfolded protein response and glycolysis. In particular, GAPDH and ENO1, critical enzymes in glycolysis, showed the highest interaction degree in the protein-protein interaction network of ARDS. In the discovery cohort, a panel of 36 proteins was identified as candidate biomarkers, with 8 proteins (VCAM1, LDHB, MSN, FLG2, TAGLN2, LMNA, MBL2, and LBP) demonstrating significant consistency in an independent validation cohort of 183 patients (mean age 72.6 years, 73.2% male), confirmed by PRM assay. The protein-based model exhibited superior predictive accuracy compared to the clinical model in both the discovery cohort (AUC: 0.893 vs. 0.784; Delong test, P < 0.001) and the validation cohort (AUC: 0.802 vs. 0.738; Delong test, P = 0.008). INTERPRETATION: Our multi-omics study demonstrated the potential biological mechanism and therapy targets in ARDS. This study unveiled several novel predictive biomarkers and established a validated prediction model for the poor prognosis of ARDS, offering valuable insights into the prognosis of individuals with ARDS.

[Effect of Vegetation Restoration on Soil Organic Carbon Storage in Coal Mining Areas Based on Meta-analysis].

Coal mining is the world's primary means of coping with an increasing energy demand. However, with the mining of coal, the regional ecosystem has been damaged to varying degrees, resulting in a decrease in the "carbon sink" capacity. Vegetation restoration is the basis for the restoration of degraded ecosystems and carbon sequestration functions in mining areas. However, no systematic studies have been conducted on the effects of vegetation restoration on soil organic carbon in coal mining areas on a global scale. Therefore, it is not possible to accurately predict the response of the global SOC pool to vegetation restoration. In this study, soil physicochemical properties of vegetation restoration were collected from 112 peer-reviewed articles to assess the effects of vegetation restoration type, soil depth, restoration year, mean annual temperature, annual precipitation, and elevation on soil organic carbon in coal mining areas and to identify relevant key drivers. The results showed that the damaged coal mine area could significantly improve the physicochemical properties of the soil through vegetation restoration. The restored soils had 39.02% higher SOC reserves compared to that in unrestored or naturally restored soils. When environmental factors were not considered, the vegetation restoration types that were favorable for SOC stock accumulation were cropland > woodland > grassland > shrubland. All four types of vegetation restoration significantly increased the SOC storage in the surface layer (0-20 cm). Grassland and shrubs significantly increased SOC storage at depth (>40 cm), whereas SOC storage at depth under woodland and farmland types was not significantly different from SOC storage after unrestored or natural restoration. The increasing trend of SOC storage after vegetation restoration decreased with increasing soil depth. The specific vegetation restoration strategy should select the appropriate vegetation type according to the climatic conditions. The types of vegetation restoration with higher carbon sequestration effects in damaged coal mining areas with mean annual temperature <0℃ and mean annual precipitation <500 mm were grassland or shrubland. In contrast, woodland and cropland restoration types could better increase SOC storage in environments with mean annual temperature >15℃ and annual precipitation >800 mm. TN, BD, AN, and AK were the main factors influencing the ability to affect soil carbon sequestration. This study can provide a theoretical reference for quantifying the carbon sequestration effects of different vegetation restoration measures in damaged coal mining areas and the restoration and reconstruction of degraded ecosystems.

Cell-free DNA predicts all-cause mortality of sepsis-induced acute kidney injury.

Background Sepsis-induced acute kidney injury (S-AKI) is a common complication in critically ill patients. Therefore, reliable biomarkers for predicting S-AKI outcomes are necessary. Serum cell-free DNA (cfDNA) is a circulating extracellular DNA fragment used as a noninvasive screening tool for many diseases, including sepsis. This study aimed to investigate the prognostic value of cfDNA in S-AKI patients and its relationship with some other parameters.Methods A total of 89 S-AKI patients admitted to the intensive care unit (ICU) from June 2021 to December 2021 were enrolled in this study. The patients were categorized into the low cfDNA group (< 855 ng/ml) and high cfDNA group (≥ 855 ng/ml) and were followed up for three months. CfDNA was extracted from serum and quantified using Quant-iT PicoGreen dsDNA Reagent.Results Overall survival was significantly lower in the high cfDNA group than in the low cfDNA group (Log-Rank p = 0.012). Univariate Cox proportional hazard model showed that cfDNA was significantly associated with all-cause mortality (HR [hazard ratio] 2.505, 95% CI [95% confidence interval] 1.184-5.298, p = 0.016). Also, serum cfDNA was a significant risk factor for all-cause mortality after adjusting for covariates (HR 2.191, 95% CI 1.017-4.721, p = 0.045). Moreover, cfDNA was positively correlated with several baseline parameters, including serum creatine, aspartate aminotransferase, alanine aminotransferase, prothrombin time, and International Normalized Ratio.Conclusion High serum cfDNA level is associated with higher mortality among the S-AKI population, indicating that cfDNA is a valuable biomarker for S-AKI prognosis.

Case series of ovarian neuroendocrine carcinoma: overview of clinicopathological features.

BACKGROUND: Ovarian neuroendocrine carcinoma (O-NEC) is a relatively uncommon neoplasm, and the current knowledge regarding its diagnosis and management is limited. In this series, our objective was to provide an overview of the clinicopathological characteristics of the disease by analyzing clinical case data to establish a theoretical foundation for the diagnosis and management of O-NEC. CASE PRESENTATION: We included three patients in the present case series, all of whom were diagnosed with primary O-NEC based on pathomorphological observation and immunohistochemistry. Patient 1 was a 62-year-old patient diagnosed with small cell carcinoma (SCC) of the pulmonary type. Post-surgery, the patient was diagnosed with stage II SCC of the ovary and underwent standardized chemotherapy; however, imaging examinations conducted at the 16-month follow-up revealed the existence of lymph node metastasis. Unfortunately, she passed away 21 months after the surgery. The other two patients were diagnosed with carcinoid tumors, one at age 39 and the other at age 71. Post-surgery, patient 2 was diagnosed with a carcinoid in the left ovary, whereas patient 3 was diagnosed with a carcinoid in her right ovary based on clinical evaluation. Neither of the cases received adjuvant therapy following surgery; however, they have both survived for 9 and 10 years, respectively, as of date. CONCLUSION: Primary O-NECs are rare and of diverse histological types, each of which has its own unique biological features and prognosis. SCC is a neoplasm characterized by high malignancy and a poor prognosis, whereas carcinoid tumors are of lesser malignancy and have a more favorable prognosis.

A follow-up study on the recovery and reinfection of Omicron COVID-19 patients in Shanghai, China.

Limited follow-up data is available on the recovery of Omicron COVID-19 patients after acute illness. It is also critical to understand persistence of neutralizing antibody (NAb) and of T-cell mediated immunity and the role of hybrid immunity in preventing SARS-CoV-2 reinfection. This prospective cohort study included Omicron COVID-19 individuals from April to June 2022 in Shanghai, China, during a large epidemic caused by the Omicron BA.2 variant. A total of 8945 patients from three medical centres were included in the follow up programme from November 2022 to February 2023. Of 6412 individuals enrolled for the long COVID analysis, 605 (9.4%) individuals experienced at least one sequelae, mainly had fatigue and mental symptoms specific to Omicron BA.2 infection compared with other common respiratory tract infections. During the second-visit, 548 (12.1%) cases of Omicron reinfection were identified. Hybrid immunity with full and booster vaccination had reduced risk of SARS-CoV-2 reinfection by 0.29-fold (95% CI: 0.63-0.81) and 0.23-fold (95% CI: 0.68-0.87), respectively. For 469 participants willing to the hospital during the first visit, those who received full (72 [IQR, 36-156]) or booster (64 [IQR, 28-132]) vaccination had significantly higher neutralizing antibody titers than those with incomplete vaccination (36 [IQR, 16-79]). Moreover, non-reinfection cases had higher neutralizing antibody titers (64 [IQR, 28-152]) compared to reinfection cases (32 [IQR, 20-69]).

The delaying effect of Qingxin Zishen decoction on ovarian aging: Examining regulation of ovarian mitochondria apoptosis in aged rats.

Ovarian aging is a significant challenge in gynecology, and there is currently no effective treatment for it. However, the medicinal agent Qingxin Zishen decoction (QZD) has shown potential in the treatment of ovarian dysfunction. The present study aimed to evaluate the mitochondrial apoptotic mechanism of delayed ovarian aging in QZD in aging rats. The healthy female Sprague-Dawley (SD) rats (n = 40, 350 ± 20 g) were randomly assigned to different dosage groups and 4-month-old SD rats (n = 10) were assigned to the control group. QZD groups were treated with QZD for four weeks, and ovarian tissues were extracted for mRNA and protein assays to examine the role of the apoptotic pathway in QZD. The results showed that QZD treatment for four weeks significantly increased the mRNA and protein expressions of the anti-apoptotic gene B-cell lymphoma 2 (Bcl-2) and Bcl-2/Bax ratio, as well as downregulated the pro-apoptotic genes Bax, caspase-3, and caspase-9. Moreover, QZD treatment effectively reduced the expression of cytochrome C (cyto-C) and apoptotic protease-activating factor 1 (Apaf-1), both of which are components of the intrinsic apoptotic pathway. These changes exhibited a dose-response manner. The findings suggest that QZD might have therapeutic potential in delaying ovarian mitochondrial function decline and in preventing and treating ovarian aging-related diseases by downregulating and upregulating the pro-apoptotic (Bax, caspase-3, caspase-9, cyto-C, Apaf-1) and anti-apoptotic (Bcl-2 and Bcl-2/Bax ratio) genes, respectively.

SBHA: Sensitive Binary Hashing Autoencoder for Image Retrieval.

Binary hashing is an effective approach for content-based image retrieval, and learning binary codes with neural networks has attracted increasing attention in recent years. However, the training of hashing neural networks is difficult due to the binary constraint on hash codes. In addition, neural networks are easily affected by input data with small perturbations. Therefore, a sensitive binary hashing autoencoder (SBHA) is proposed to handle these challenges by introducing stochastic sensitivity for image retrieval. SBHA extracts meaningful features from original inputs and maps them onto a binary space to obtain binary hash codes directly. Different from ordinary autoencoders, SBHA is trained by minimizing the reconstruction error, the stochastic sensitive error, and the binary constraint error simultaneously. SBHA reduces output sensitivity to unseen samples with small perturbations from training samples by minimizing the stochastic sensitive error, which helps to learn more robust features. Moreover, SBHA is trained with a binary constraint and outputs binary codes directly. To tackle the difficulty of optimization with the binary constraint, we train the SBHA with alternating optimization. Experimental results on three benchmark datasets show that SBHA is competitive and significantly outperforms state-of-the-art methods for binary hashing.

Dual roles of TRIM3 in colorectal cancer by retaining p53 in the cytoplasm to decrease its nuclear expression.

Colorectal cancer is a very heterogeneous disease caused by the interaction of genetic and environmental factors. P53, as a frequent mutation gene, plays a critical role in the adenoma-carcinoma transition during the tumorous pathological process. Our team discovered TRIM3 as a tumor-associated gene in CRC by high-content screening techniques. TRIM3 demonstrated both tumor-suppressive and tumorigenic features in cell experiments dependent on the cell status of wild or mutant p53. TRIM3 could directly interact with the C terminus of p53 (residues 320 to 393), a common segment of wtp53 and mutp53. Moreover, TRIM3 could exert different neoplastic features by retaining p53 in the cytoplasm to decrease its nuclear expression in a wtp53 or mutp53-dependent pathway. Chemotherapy resistance develops in nearly all patients with advanced CRC and seriously limits the therapeutic efficacies of anticancer drugs. TRIM3 could reverse the chemotherapy resistance of oxaliplatin in mutp53 CRC cells by degradation of mutp53 in the nuclei to downregulate the multidrug resistance gene. Therefore, TRIM3 could be a potential therapeutic strategy to improve the survival of CRC patients with mutp53.

Associations between sex differences, eating disorder behaviors, physical and mental health, and self-harm among Chinese adolescents.

BACKGROUND AND AIM: Eating Disorders (ED) result in impaired well-being, but there exist an insufficient number of studies that have focused on the influence of sex and sexual orientation disparities within ED behaviors. Thus, we aimed to investigate ED behaviors among male and female adolescents with different sexual orientations in a school sample to understand prevalence and correlates of different ED behaviors. METHOD: Data was analysed from 11,440 Chinese school adolescents with a mean age of 14.74 years (SD = 1.46). Reported data was gathered on sociodemographic information including sexual orientation, ED behaviors, health factors (reported health, cognitive function), mental health factors (depression, anxiety, suicidal ideation, non-suicidal self-injurious behavior), and social functioning (school bully victimization, and school bully perpetration). Logistic regression models were used to estimate the associations with ED behaviors, using the heterosexual orientation as the reference group as they are the majority. RESULTS: Compared to female adolescents, male adolescents reported lower anxiety symptoms (t = - 12.39, p < 0.001, Cohen's d = - 0.233), were more likely to be the perpetrator of school bullying (χ2 = 190.61, p < 0.001, φ = 0.129), and reported a lower likelihood of taking dietary restriction (χ2 = 290.08, p < 0.001, φ = 0.160). Overall, the prevalence of dietary restriction presented sex disparities. Adolescents who reported no sexual attraction were less likely to engage in ED behaviors. Using heterosexual orientation as the reference group, the group who reported no sexual attraction was associated with lower risk in dietary restriction and purging in both male and female adolescents. Using the heterosexual orientation as the reference group, female sexual minority groups were at high risk of ED behaviors, with bisexual orientation and gay/lesbian orientation having a higher likelihood of engaging in objective binge eating. CONCLUSIONS: The results revealed significant sex and sexual orientation differences of ED behaviors. The study suggests that adolescents is a period of sexuality development and could be critical for understanding adolescents' eating behaviors. It is important to guide adolescents to healthy eating during their development and considerations should be made by clinicians when creating interventions for ED behaviors among the different sex and sexual orientation groups.

CEBPB regulates the migration, invasion and EMT of breast cancer cells by inhibiting THBS2 expression and O-fucosylation.

Breast cancer (bc) is the second most common type of human malignancies with highest morbidity and mortality in the female population. Therefore, it is essential to develop novel and effective therapies for bc treatment. The main aim of the current study is to investigate the functions of CEBPB and THBS2 in bc and the underlying mechanism. Reverse transcription-quantitative real-time polymerase chain reaction and western blot were performed for the measurement of ribonucleic acids and proteins. Function and mechanism assays were, respectively, conducted for the evaluation of bc biological behaviors and exploration of the potential correlation of genes. According to bioinformatics analyses and experimental results, THBS2, up-regulated in bc tissues and cell lines, could facilitate cell migration, invasion and EMT in bc. CEBPB was validated to facilitate miR-29a-3p transcription, thus negatively modulating THBS2 expression. The results of rescue experiments reflected that CEBPB could regulate the malignant behaviors of bc cells via THBS2. Furthermore, CEBPB was ascertained to inhibit the transcription of B3GALTL to affect THBS2 protein O-fucosylation and secretion. The interaction between THBS2 and ITGB1 was confirmed, and THBS2 was found to activate the PI3K/AKT signaling pathway. To conclude, CEBPB could restrain bc cell migration, invasion and EMT via inhibition on THBS2 expression and O-fucosylation.

Generalized Knowledge Distillation via Relationship Matching.

The knowledge of a well-trained deep neural network (a.k.a. the "teacher") is valuable for learning similar tasks. Knowledge distillation extracts knowledge from the teacher and integrates it with the target model (a.k.a. the "student"), which expands the student's knowledge and improves its learning efficacy. Instead of enforcing the teacher to work on the same task as the student, we borrow the knowledge from a teacher trained from a general label space - in this "Generalized Knowledge Distillation (GKD)," the classes of the teacher and the student may be the same, completely different, or partially overlapped. We claim that the comparison ability between instances acts as an essential factor threading knowledge across tasks, and propose the RElationship FacIlitated Local cLassifiEr Distillation (stance-label confidence between models, ReFilled requires the teacher to reweight the hard tuples pushed forward by the student and then matches the similarity comparison levels between instances. An embedding-induced classifier based on the teacher model supervises the student's classification confidence and adaptively emphasizes the most related supervision from the teacher. ReFilled demonstrates strong discriminative ability when the classes of the teacher vary from the same to a fully non-overlapped set w.r.t. the student. It also achieves state-of-the-art performance on standard knowledge distillation, one-step incremental learning, and few-shot learning tasks.

A Characterization of Brain Area Activation in Orienteers with Different Map-Recognition Memory Ability Task Levels-Based on fNIRS Evidence.

BACKGROUND: Mapping memory ability is highly correlated with an orienteer's level, and spatial memory tasks of different difficulties can reveal the spatial cognitive characteristics of high-level athletes. METHODS: An "expert-novice" experimental paradigm was used to monitor behavioral performance and changes in cerebral blood oxygen concentration in orienteering athletes with tasks of different difficulty and cognitive load using functional near-infrared spectroscopic imaging (fNIRS). RESULTS: (1) there was no difference between high-/low-level athletes' map recognition and memory abilities in the non-orienteering scenario; (2) with increasing task difficulty, both high-/low-level athletes showed significantly decreasing behavioral performance, reduced correctness, longer reaction time, and strengthened cerebral blood oxygen activation concentration. There was no significant difference in L-DLPFC cerebral oxygen concentration between high-/low-level athletes in the simple map task, and the cerebral oxygen concentration in all brain regions was lower in the expert group than in the novice group in the rest of the task difficulty levels; (3) the correctness rate in the expert group in the complex task was closely related to the activation of the right hemisphere (R-DLPFC, R-VLPFC). CONCLUSIONS: Experts have a specific cognitive advantage in map-recognition memory, showing higher task performance and lower cerebral blood oxygen activation; cognitive load constrains map-recognition memory-specific ability and produces different performance effects and brain activation changes on spatial memory processing.

Aerobic exercise regulates FGF21 and NLRP3 inflammasome-mediated pyroptosis and inhibits atherosclerosis in mice.

Fibroblast growth factor 21 (FGF21), a known risk factor for atherosclerosis, is readily regulated by exercise, and it can inhibit NOD-like receptor protein 3 (NLRP3)-mediated pyroptosis. However, it is not clear whether aerobic exercise inhibits atherosclerosis via these pathways. Eight-week-old apolipoprotein E-deficient (ApoE-/-) mice on a high-fat diet were randomly divided into 1-h post-exercise (EX-1h), 24-h post-exercise (EX-24h), and sedentary (SED) groups. C57BL/6J wild-type mice fed normal chow served as controls (WT group). Mice in the EX-1h and EX-24h groups were subjected to treadmill exercise training for 12 weeks. Aerobic exercise reduced body weight; blood glucose, lipid, and inflammation levels; and aortic plaque area proportion. Aerobic exercise increased the sensitivity of FGF21 by upregulating the expression of the downstream receptor adiponectin (ApN); the serum FGF21 level after exercise increased initially, and then decreased. Aerobic exercise downregulated the expression of NLRP3 inflammasome-mediated pyroptosis-related markers in the aorta, and FGF21 may participate in the above process. Meanwhile, the liver may be the tissue source of serum FGF21 during aerobic exercise. In conclusion, aerobic exercise may inhibit atherogenesis by regulating FGF21 and NLRP3 inflammasome-mediated pyroptosis. Our study provides new information on the atherosclerosis-preventing mechanism of aerobic exercise.

Immune-Related LncRNAs as Prognostic Factors for Pediatric Rhabdoid Tumor of the Kidney.

Background: Immune-related long noncoding RNAs (IrlncRNAs) are recognized as important prognostic factors in a variety of cancers, but thus far, their prognostic value in pediatric rhabdoid tumor of the kidney (pRTK) has not been reported. Here, we clarified the associations between IrlncRNAs and overall survival (OS) of pRTK patients and constructed a model to predict their prognosis. Methods: We accessed RNA sequencing data and corresponding clinical data of pRTK from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. An expression profile of immune-related genes (Irgenes) and lncRNAs of pRTK was extracted from the RNA sequencing data. IrlncRNAs were defined by co-expression analysis of lncRNAs and Irgenes. The limma R package was used to identify differential expression IrlncRNAs. Univariate and multivariate Cox regression analyses were conducted to build a prognostic IrlncRNAs model. The performance of this prognostic model was validated by multimethods, like ROC curve analysis. Results: A total of 1097 IrlncRNAs were defined. Univariate Cox regression analysis identified 7 IrlncRNAs (AC004791.2, AP003068.23, RP11-54O7.14, RP11-680F8.1, TBC1D3P1-DHX40P1, TUNAR, and XXbac-BPG308K3.5) and were significantly associated with OS. Multivariate regression analysis constructed the best prognostic model based on the expression of AC004791.2, AP003068.23, RP11-54O7.14, TBC1D3P1-DHX40P1, and TUNAR. According to the prognostic model, a risk score of each patient was calculated, and patients were divided into high-risk and low-risk groups accordingly. The survival time of low-risk patients was significantly better than high-risk patients (p < 0.001). Univariate (hazard ratio 1.098, 95% confidence interval 1.048-1.149, p value <0.001) and multivariate (hazard ratio 1.095, 95% confidence interval 1.043-1.150, p value <0.001) analyses confirmed that the prognostic model was reliable and independent in prediction of OS. Time-dependent ROC analysis showed that 1-year survival AUC of prognostic model, stage, age, and sex was 0.824, 0.673, 0.531, and 0.495, respectively, which suggested that the prognostic model was the best predictor of survival in pRTK patients. Conclusions: The prognostic model based on 5 IrlncRNAs was robust and could better predict the survival of pRTK than other clinical factors. Additionally, the mechanism of regulation and action of prognosis-associated lncRNAs could provide new avenues for basic research to explore the mechanism of tumor initiation and development in order to prevent and treat pRTK.

Genetic and hosts characterization of hantaviruses in port areas in Hainan Province, P. R. China.

BACKGROUND: Hantaviruses (HVs) are major zoonotic pathogens in China that cause hemorrhagic fever with renal syndrome (HFRS) posing a major threat to people's health. Hainan Province, an island located in Southeast China, is an ideal region for sea ports. The unique tropical monsoon climate in Hainan provides sufficient living conditions for rodents, which help spread HVs and other rodent-borne diseases. In the routine monitoring of hantavirus, there was no evidence that rodents in Hainan carried hantavirus. No patients infected with hantavirus were found in the past. However, the surveillance of HVs-carrying rodents covering the whole territory of Hainan has not stopped. METHODOLOGY/PRINCIPAL FINDINGS: For the monitoring of the prevalence of HVs in rodents and the search for theoretical reference for rodent control and HFRS prevention, a total of 60 rodents from 6 monitoring spots were trapped around main ports in Hainan between 2016 and 2019. HV positive samples were identified by a specific kit and sequenced. The data indicated that seven rodents (Rattus norvegicus) were positive for hantavirus with a positivity rate of 11.67%. Phylogenetic analysis suggested that the two complete sequence strains HN1 and HN4 in this research were highly similar to the sequence strains GZRn36 and GZRn148 isolated in Guangdong Province, and they located in the same phylogenetic tree branch which belongs to S2 subtype. Although the two partial sequences HT1 and HT2 isolated in Xisha Islands belong to S2 subtype according to the phylogenetic tree of L segment, they showed a great nucleotide difference with HN1 and HN4. We also found 13 amino acid variations compared with SEOV 80-39 and 6 amino acid mutations related to epitope, and the variations may reduce the effectiveness of the current HFRS vaccines used in humans. CONCLUSIONS/SIGNIFICANCE: The study indicated HVs carried by rodents found in Hainan Province may be transmitted from Guangdong Province through trading ports and carriage of goods by sea. So it is of great significance to strengthen the surveillance of rodents in port areas especially capture and eliminate rodents on ship. Timely elimination of host animals of hantavirus in port areas is necessary to prevent an outbreak of HVs disease.

PGM5P3-AS1 regulates MAP1LC3C to promote cell ferroptosis and thus inhibiting the malignant progression of triple-negative breast cancer.

PURPOSE: Triple-negative breast cancer (TNBC) represents an aggressive subtype of breast cancer characteristic of high recurrence rate and poor prognosis. According to previous studies and bioinformatics prediction, PGM5P3-AS1 has been found to be significantly down-regulated in TNBC cells. In addition, cell ferroptosis has become a hotspot in breast cancer research and TNBC has been reported to be more sensitive to ferroptosis than receptor positive breast cancer. Hence, we aim at exploring the molecular mechanism of PGM5P3-AS1 in TNBC cells and further explore whether PGM5P3-AS1 can inhibit TNBC progression via promoting cell ferroptosis. METHODS: The expression of genes in TNBC cells was verified by RT-qPCR assay. Functional assays were taken to evaluate the impact PGM5P3-AS1 may exert on TNBC progression. The regulatory pattern of PGM5P3-AS1 on cell ferroptosis in TNBC was validated through mechanism assays. RESULTS: PGM5P3-AS1 was proved to be down-regulated in TNBC cells and suppressed TNBC cell proliferation as well as migration. PGM5P3-AS1 promoted cell ferroptosis in TNBC by recruiting RNA-binding protein (RBP) NOP58 to stabilize MAP1LC3C mRNA, and thus inhibiting TNBC progression. CONCLUSION: PGM5P3-AS1 regulated MAP1LC3C to promote cell ferroptosis and thus inhibiting the malignant progression of TNBC.

circRNA RPPH1 Facilitates the Aggravation of Breast Cancer Development by Regulating miR-542-3p/ARHGAP1 Pathway.

Background: Circular RNAs (circRNAs) have important roles in human malignancies, including breast cancer (BC). In this study, we explored the function of circRNA ribonuclease P RNA component H1 (circ_RPPH1) in BC development and clarify the mechanistic pathway. Materials and Methods: Expression of circ_RPPH1, microRNA-542-3p (miR-542-3p), and Rho GTPase-activating protein 1 (ARHGAP1) in BC tissues and cells was determined by quantitative real-time polymerase chain reaction or Western blot assay. The stability of circ_RPPH1 was confirmed by RNase R and actinomycin D treatment. Cell viability and colony formation ability were measured by methyl thiazolyl tetrazolium (MTT) assay and colony formation assay, respectively. Western blot analysis was also used to detect proliferation biomarker (Ki67) and epithelial-mesenchymal transition (EMT) biomarkers (E-cadherin, N-cadherin, and vimentin). Flow cytometry and Transwell assays were performed to monitor cell apoptosis, migration, and invasion. The binding potency between miR-542-3p and circ_RPPH1 or ARHGAP1 was validated by dual-luciferase reporter assay. Functional role of circ_RPPH1 in vivo was investigated by xenograft tumor reporter assay. Results: Upregulation of circ_RPPH1 and ARHGAP1, and downregulation of miR-542-3p were detected in BC tissues and cells. circ_RPPH1 knockdown or miR-542-3p introduction inhibited BC cell proliferation and metastasis, while promoted apoptosis in vitro. circ_RPPH1 sponged miR-542-3p to upregulate ARHGAP1 expression, thereby affecting BC progression. Moreover, depletion of circ_RPPH1 suppressed tumor growth in vivo. Conclusions: circ_RPPH1 contributed to BC tumorigenesis by sponging miR-542-3p and upregulating ARHGAP1, affording a novel mechanistic pathway in BC development.

Protective effect of antioxidant peptides from grass carp scale gelatin on the H2O2-mediated oxidative injured HepG2 cells.

The protective effect of antioxidant peptides from grass carp scale gelatin on hydrogen peroxide (H2O2)-mediated oxidative injured HepG2 cells was investigated, and the protective mechanism as well as peptide structure were studied. Pretreated with grass carp scale gelatin hydrolysates (GSGH) for 24 h significantly increased the survival rates and decreased the apoptosis rates of H2O2-mediated oxidative injured HepG2 cells. The increase in SOD, CAT and GPX activities, reduce in ROS level and MDA content, and weaken in damage on cell membrane and DNA could be responsible for the protective effect of GSGH on H2O2-mediated oxidative injured HepG2 cells. Peptide sequences of GSGH were analyzed by LC-ESI-Q-Orbitrap-MS/MS, and results showed that most of them were low molecular weight peptide at 358-986 Da. Synergistic effect existed among antioxidant peptides and contributed to the strong antioxidant activities of GSGH.

Long Noncoding-RNA Component of Mitochondrial RNA Processing Endoribonuclease Promotes Carcinogenesis in Triple-Negative Breast Cancer Cells via the Competing Endogenous RNA Mechanism.

PURPOSE: Triple-negative breast cancer (TNBC) is a subtype of breast cancer. Increasing evidence supports that dysregulation of long noncoding RNAs (lncRNAs) plays a vital role in cancer progression. RNA component of mitochondrial RNA processing endoribonuclease (RMRP), a lncRNA, is characterized as a tumor-propeller in some cancers, but its mechanism in TNBC remains poorly understood. This study aimed to determine whether and how RMRP functions in TNBC. METHODS: Cell proliferation was determined by cell counting kit-8 (CCK-8) and colony formation assays and cell apoptosis by flow cytometry analysis and terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. Cell migration and invasion were determined by transwell assays. RNA-binding protein immunoprecipitation (RIP), luciferase reporter, and RNA pulldown assays were implemented to assess the interaction of RMRP with other molecules in TNBC cells. RESULTS: RMRP expression was elevated in TNBC cells. RMRP knockdown repressed cell proliferation, migration, and invasion, but induced apoptosis in TNBC. In addition, RMRP was found to target microRNA-766-5p (miR-766-5p) in TNBC cells. Silencing miR-766-5p enhanced cell viability and decreased apoptosis, whereas miR-766-5p overexpression had opposite effects. Furthermore, miR-766-5p was found to bind to yes-associated protein 1 (YAP1). Moreover, miR-766-5p inhibition reversed the repressive effect of RMRP knockdown on the malignant progression of TNBC. CONCLUSION: The present study manifested that RMRP promotes the growth, migration, and invasion of TNBC cells via the miR-766-5p/YAP1 axis. These findings provide novel perspectives for TNBC treatment.